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1.  Immunohistochemical (IHC) Analysis of Non-Hodgkin’s Lymphoma (NHL) Spectrum According to WHO/REAL Classification: A Single Centre Experience from Punjab, India 
Introduction: The distribution of the major subtypes of non-Hodgkin’s lymphoma (NHL) differs across geographic regions. This study, from the north Indian state of Punjab, has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes based on World Health Organization (WHO)/ Revised European-American Classification of Lymphoid Neoplasms (REAL) system of classification.
Patients and methods: Over all seventy seven cases of lymphoma over a period of one year (between April 2012 and April 2013) were diagnosed in the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar (Punjab). Of these 30 cases (39%) were of Hodgkin’s Lymphoma (HL) and 47 cases (61%) were of Non Hodgkins lymphoma NHL.
Of the total of cases of lympho-proliferative disorders, the diagnosis of NHL was done by light microscopy alone. All the cases diagnosed provisionally as NHL were taken up for immunophenotyping with Immunohistochemical (IHC) studies. There was 100 % concordance between the light microscopy and IHC studies.
The individual NHL cases were classified according to the WHO/REAL classification according to the positive or relevant negative immonophenotypic expression and tabulated to ascertain the morphological spectrum of NHL in this part of the country.
Results: B-cell lymphomas formed 89.3%, whereas T-cell lymphomas formed 10.7% of the NHLs. Diffuse Large B-Cell Lymphoma (DLBCL) was the most common subtype (46.8% of all NHLs). B-cell small lymphocytic lymphoma, Mantle-Cell Lymphoma (MCL), marginal zone B-cell lymphomas (including MALT lymphomas), Diffuse, mixed small cleaved cell and large-cell type and Follicular centre-cell lymphomas amounted to 17%, 12.8%, 2.1%, 2.1% and 4.3%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and Angioimmunoblastic T-cell lymphoma (AITL) accounted for 6.4%, 2.1%, and 2.1% of all NHL cases, respectively.
Conclusions: The distribution of NHL subtypes in India shows disparity with those from the rest of the world. Follicular Lymphoma (FL) and MCL are less common in India compared to Europe and the USA. Peripheral T-cell lymphomas and T/NK-cell lymphomas of nasal and nasal types, which are common in many other Asian countries, are also less prevalent. T-cell lymphoblastic lymphoma and anaplastic large T/null cell lymphoma are more prevalent in India.
doi:10.7860/JCDR/2014/8173.3988
PMCID: PMC3939585  PMID: 24596721
Non Hodgkins lymphoma; WHO/REAL classification; Immunophenotyping; B-cell lymphomas; T-cell lymphomas
2.  Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL) 
BMC Cancer  2011;11:321.
Background
Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.
Methods
We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.
Results
B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.
Conclusions
The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.
doi:10.1186/1471-2407-11-321
PMCID: PMC3160411  PMID: 21798075
intestine; non-Hodgkin lymphoma; prognosis; histopathology
3.  Maltoma of Thyroid: A Rare Thyroid Tumour 
Case Reports in Otolaryngology  2013;2013:740241.
Introduction. Primary thyroid lymphomas constitute up to 5% of all thyroid malignancies and can be divided into non-Hodgkin's lymphomas (NHLs) of B- and T-cell types, as well as Hodgkin's lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphomas are a relatively recently recognized subset of B-cell NHLs, and they are listed as extranodal marginal zone lymphomas according to the revised European-American lymphoma classification. Case Report. We report an uncommon case of a 44-year-old man, who noted a painless, growing mass on right side of his neck of the three-month duration. Thyroid profile was within normal limits. FNAC showed lymphocytic thyroiditis. The patient underwent a right hemithyroidectomy. The histologic examination and the immunohistochemistry showed an extra nodal marginal B-cell type maltoma (malt lymphoma). CHOP chemotherapy with rituximab was given. The clinical course has been favourable in the first year of followup, with no evidence of local or systemic recurrence of the disease. Discussion. Marginal zone lymphoma encompasses a heterogeneous group of B-cell tumours that variously arise within the lymph nodes, spleen, or extranodal tissues. A case of maltoma of thyroid is presented for its rarity and diagnostic dilemmas. Conclusion. Maltomas are slow-growing lymphomas. The optimal treatment and followup of patients with thyroid maltomas remain controversial at present.
doi:10.1155/2013/740241
PMCID: PMC3582082  PMID: 23476858
4.  Long term outcome of ocular adnexal lymphoma subtyped according to the REAL classification 
AIM—To classify ocular adnexal lymphomas according to the Revised European and American Lymphoma (REAL) classification and to determine any correlation between clinical features or histomorphological variables with the patients' outcome.
METHODS—Conventional and immunohistology were performed on representative sections of 53 specimens of 46 patients with ocular adnexal lymphoma. The antibodies used were CD20, BCL-2, CD21, CD23, CD43, CD3, CD5, p53, cyclin D1, pan-cytokeratin, kappa, lambda, IgD, and IgM. The growth fraction of the tumours was determined using the MIB-1 antibody directed against the Ki-67 antigen. Clinical follow up data regarding the outcome were obtained from the treating physicians and/or hospital files. The Student's t test and log rank test were used for statistical analysis.
RESULTS—The patient collective consisted of 29 females and 17 males with an age range of 32-89.7 years (average 63 years). Almost all specimens represented B cell non-Hodgkin's lymphomas: extranodal marginal zone lymphoma (EMZL) (n=38), diffuse large cell B cell lymphoma (n=8), lymphoplasmocytic lymphoma/immunocytoma (n=2), mantle cell lymphoma (n=2), follicle centre lymphoma (n=1), and plasmacytoma (n=1). One case of a secondary anaplastic large cell lymphoma of T cell type (T-ALCL) was diagnosed. The majority of the patients had stage I disease. A variety of therapeutic regimens was administered, the main form of treatment being radiotherapy. The average follow up time was 85 months. Complete remission was achieved in 24 patients (10 after excision alone, eight after radiotherapy alone, three after combined excision and radiotherapy, one after chemotherapy alone, and two after combined radiotherapy and chemotherapy). 12 patients died of causes related to lymphoma; in one patient the cause of death was unknown. Six patients had persistent tumour at final follow up and two patients were lost to follow up. The stage at presentation, as well as the lymphoma malignancy category, had a significant correlation with the final course of the disease (p=0.0001 and p=0.03, respectively). A significant correlation was also noted between the final outcome (p<0.05) and tumour cell expression for Ki-67 antigen and p53 protein.
CONCLUSION—67% of patients with ocular adnexal lymphoma had EMZL. The stage at presentation had a significant influence on the final outcome. MIB-1 and p53 expression by the tumour cells proved to be important immunohistochemical markers concerning the prognosis. It is suggested that, following thorough staging investigations, primary EMZL (stage I) (if accessible) should be treated with excisional biopsy and subsequent low dose radiotherapy. Primary diffuse large cell B cell lymphoma of the ocular adnexa requires at least similar therapeutic measures and regular intensive follow up.


doi:10.1136/bjo.85.1.63
PMCID: PMC1723704  PMID: 11133714
5.  Analysis of clinical characteristics, diagnosis, treatment and prognosis of 46 patients with primary gastrointestinal non-Hodgkin lymphoma 
Molecular and Clinical Oncology  2013;2(2):259-264.
Primary gastrointestinal non-Hodgkin lymphoma (PGI NHL) is one of the most common types of extranodal lymphoma, accounting for ~30–50% of all extranodal lymphomas. The aim of the present study was to investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with PGI NHL. A total of 46 patients with PGI NHL (mean age, 50 years) were enrolled in this study, with a male:female ratio of 1.3:1. The most common site of PGI NHL was the stomach (52.2%), followed by the colon (34.8%) and small intestine (8.7%). The most common symptoms of PGI NHL included abdominal pain or discomfort (91.3%), loss of appetite (65.2%) and weight loss (56.5%) and the most common pathological subtype of PGI NHL was diffuse large B-cell lymphoma (DLBCL) (78.3%). Lesions were identified in 95.7% of PGI NHL patients under preoperative endoscopic examination, whereas the diagnosis rate was only 21.7% during preoperative endoscopic biopsy. All 46 patients underwent surgical treatment and 36 also received postoperative chemotherapy or radiotherapy. The follow-up time was 6–70 months in 37 PGI NHL patients, with 1-, 3- and 5-year survival rates of 81.1, 62.16 and 50.0%, respectively. The 5-year survival rate differed significantly according to clinical stage (P=0.002) and tumor size (P=0.0017) among patients with PGI NHL. However, there was no statistically significant difference in the 5-year survival rate between patients who received surgery alone and those who received surgery plus postoperative chemotherapy or radiotherapy (P=0.1371). Furthermore, there were no statistically significant differences in gender (P=0.127), clinical stage (P=0.828), histological subtype (P=1.000) and surgical modality (P=0.509) between patients with primary gastric non-Hodgkin lymphoma (PG NHL) and those with primary intestinal non-Hodgkin lymphoma (PI NHL). In conclusion, PGI NHLs are a heterogeneous group of diseases, whereas clinical stage and tumor size were identified as adverse prognostic factors of PGI NHL. Further studies, including a larger number of patients treated with surgery alone, are required in order to elucidate the precise role of surgery combined with postoperative chemotherapy or radiotherapy in the prognosis of PGI NHL.
doi:10.3892/mco.2013.224
PMCID: PMC3917777  PMID: 24649343
non-Hodgkin lymphoma; gastrointestinal lymphoma; diagnosis; therapy; prognosis
6.  Primary breast lymphomas: a multicentric experience 
Background
The Primary Breast Lymphomas (PBL) represent 0,38-0,70% of all non-Hodgkin lymphomas (NHL), 1,7-2,2% of all extranodal NHL and only 0,04-0,5% of all breast cancer. Most frequent PBLs are the diffuse large B cell lymphomas; in any case-reports MALT lymphomas lack or are a rare occurrence. Their incidence is growing. From 1880 (first breast resection for "lymphadenoid sarcoma" carried out by Gross) to the recent past the gold standard treatment for such diseases was surgery. At present such role has lost some of its importance, and it is matter of debate.
Methods
Twenty-three women affected by PBL underwent surgery. Average age was 63 years (range: 39-83). Seven suffered of hypothyroidism secondary to autoimmune thyroiditis. Fourteen patients underwent mastectomy, nine patients received quadrantectomy (average neoplasm diameter: 1,85 cm, range: 1,1-2,6 cm). In 10 cases axillary dissection was carried out. Pathologic examination revealed 16 diffuse large B cell lymphomas and 7 MALT lymphomas.
Results
Seven patients in the mastectomy group had a recurrence (50%), and all of them with diffuse large B cell lymphomas at stage II. Two of these had not received chemotherapy. No patient undergoing quadrantectomy had recurrence. In the mastectomy group disease free survival (DFS) at 5 and 10 years was 57 and 50%. Overall survival (OS) at 5 and 10 years was 71.4% and 57.1% respectively. All recurrences were systemic. DFS and OS at 5 and 10 years was 100% in the quadrantectomy group. In the patients with recurrence mortality was 85.7%. For stage IE DFS and OS at 5 and 10 years were 100%. For stage II DFS at 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62.5% respectively. For MALT lymphomas DFS and OS at 5 and 10 years were 100%. For diffuse large B cell lymphomas DFS at 5 and 10 years was 62.5% and 56.2% respectively; OS at 5 and 10 years was 75% and 62,5% respectively.
Conclusions
The role of surgery in this disease should be limited to get a definitive diagnosis while for the staging and the treatment CT scan and chemio/radioterapy are repectively mandatory. MALT PBLs have a definitely better prognosis compared to large B cell lymphomas. The surgical treatment must always be oncologically radical (R0); mastectomy must not be carried out as a rule, but only when tissue sparing procedures are not feasible. Axillary dissection must always be performed for staging purposes, so avoiding the risk of under-staging II o IE, due to the possibility of clinically silent axillary node involvement.
doi:10.1186/1477-7819-8-53
PMCID: PMC2903594  PMID: 20584320
7.  A Reappraisal of the Diagnostic and Therapeutic Management of Uncommon Histologies of Primary Ocular Adnexal Lymphoma 
The Oncologist  2013;18(7):876-884.
Lymphoma is the most common malignancy arising in the ocular adnexa, which includes conjunctiva, lachrymal gland, lachrymal sac, eyelids, orbit soft tissue, and extraocular muscles. Ocular adnexal lymphoma (OAL) accounts for 1%–2% of non-Hodgkin lymphoma and 5%–15% of extranodal lymphoma. The most common and well-studied histotype is represented by marginal zone B-cell lymphoma. This review covers the prevalence, clinical presentation, behavior, and histological and molecular features of uncommon forms of primary OAL and provides practical recommendations for therapeutic management.
Lymphoma is the most common malignancy arising in the ocular adnexa, which includes conjunctiva, lachrymal gland, lachrymal sac, eyelids, orbit soft tissue, and extraocular muscles. Ocular adnexal lymphoma (OAL) accounts for 1%–2% of non-Hodgkin lymphoma and 5%–15% of extranodal lymphoma. Histology, stage, and primary localizations are the most important variables influencing the natural history and therapeutic outcome of these malignancies. Among the various lymphoma variants that could arise in the ocular adnexa, marginal zone B-cell lymphoma (OA-MZL) is the most common one. Other types of lymphoma arise much more rarely in these anatomical sites; follicular lymphoma is the second most frequent histology, followed by diffuse large B-cell lymphoma and mantle cell lymphoma. Additional lymphoma entities, like T-cell/natural killer cell lymphomas and Burkitt lymphoma, only occasionally involve orbital structures. Because they are so rare, related literature mostly consists of anecdotal cases included within series focused on OA-MZL and sporadic case reports. This bias hampers a global approach to clinical and molecular properties of these types of lymphoma, with a low level of evidence supporting therapeutic options. This review covers the prevalence, clinical presentation, behavior, and histological and molecular features of uncommon forms of primary OAL and provides practical recommendations for therapeutic management.
doi:10.1634/theoncologist.2012-0425
PMCID: PMC3720642  PMID: 23814042
Ocular adnexal lymphoma; Diffuse large B-cell lymphoma; Follicular lymphoma; Mantle cell lymphoma; T-cell lymphoma
8.  Primary extranodal lymphomas of stomach: clinical presentation, diagnostic pitfalls and management 
Annals of Oncology  2008;19(12):1992-1999.
Gastrointestinal lymphoma is the most common form of extranodal lymphoma, accounting for 30%–40% of cases. The most commonly involved site is the stomach (60%–75% of cases), followed by the small bowel, ileum, cecum, colon and rectum. The most common histological subtypes are diffuse large B-cell lymphoma (DLBCL) and marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Helicobacter pylori infection has been implicated in the pathogenesis of MALT gastric lymphoma, but its role in gastric diffuse large B-cell non-Hodgkin's lymphoma (NHL) is controversial. The therapeutic approach for patients with gastric NHL has been revised over the last 10 years. Conservative treatment with anthracycline-based chemotherapy alone or in combination with involved-field radiotherapy has replaced gastrectomy as standard therapy in cases with DLBCL. Additionally, MALT lymphomas are mainly treated with antibiotics alone, which can induce lasting remissions in those cases associated with H. pylori infection. Nevertheless, various therapeutic aspects for primary gastric lymphomas are still controversial and several questions remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as H. pylori eradication in histological aggressive subtypes warrants better clarification.
doi:10.1093/annonc/mdn525
PMCID: PMC2733120  PMID: 18647965
diffuse large B-cell lymphomas; extranodal lymphomas; Helicobacter pylori infection; mucosa-associated lymphoid tissue; primary gastric lymphomas
9.  Increasing incidence rates, distribution and histological characteristics of primary gastrointestinal non-Hodgkin lymphoma in a North American population 
BACKGROUND:
The incidence of primary extranodal non-Hodgkin lymphoma (NHL) of the gastrointestinal (GI) tract has been on the rise.
OBJECTIVES:
To determine the incidence of primary GI NHL and distribution according to site and histological type in a large North American adult population over a 10-year period.
METHODS:
All diagnoses of GI NHL made between January 1999 and January 2009 were reviewed using a regional pathology database. Patients ≥18 years of age living within health region boundaries were included. Age- and sex-adjusted incidence rates of GI NHL according to GI site and histological type over a 10-year period were calculated and compared.
RESULTS:
A total of 149 cases of primary GI NHL were identified during the study period. Age- and sex-adjusted yearly incidence rates ranged from 0.13 per 100,000 in 1999, to 2.39 per 100,000 in 2007. Histological distribution (47% diffuse large B cell lymphoma, 24% extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type, 8% follicular and 5% mantle cell) and site distribution (47% stomach, 26% small bowel, 17% colon) were obtained with increasing annualized incidence rates for each of these sites over time. Remaining cases included multiple GI sites of involvement (9%) and esophagus (0.7%).
DISCUSSION:
Population-based GI NHL incidence rates in the present study were higher than those described elsewhere in North America and Europe. Nearly one-half showed high-grade (diffuse large B cell lymphoma) histology at diagnosis. Incidence rates for the colon exceed those described in other studies worldwide.
CONCLUSION:
Because the majority of GI NHL are diagnosed on endoscopic biopsy, clinicians and pathologists must be vigilant of this entity.
PMCID: PMC3395447  PMID: 22803021
Extranodal non-Hodgkin lymphoma; Gastrointestinal tract; Incidence
10.  Malignant lymphomas of the nasal cavity and Waldeyer's ring--clinicopathologic and immunohistochemical study. 
The clinicopathologic and immunohistochemical finding of 10 cases of nasal non-Hodgkin's lymphoma (NHL) and 23 cases of Waldeyer's ring NHL were studied. Immunohistochemically, nasal NHL expressed T-cell markers exclusively, whereas the NHL of Waldeyer's ring were of both T-cell (56.5%) and B-cell lineages (43.5%). Angioinvasiveness by tumor cells was exclusively noted in the T-lineage lymphomas. Epithelial hyperplasia, epitheliotropism by tumor cells, and extensive invasion of adjacent normal tissue were more prominent in T-cell lymphomas than in B-cell lymphomas. T-lineage lymphomas showed distant extranodal spread pattern involving the skin, soft tissue, stomach, spleen, and the liver, whereas B-lineage lymphomas tended to localize in the lymph nodes. The survival rate of Nasal NHL was similar to that of Waldeyer's ring NHL. Although not statistically significant because of small sample numbers, immunophenotype, histologic groups of monomorphic lymphoma, and stage had prognostic importance. In general, T-lineage lymphomas presented with a higher stage than B-lineage lymphomas (p < 0.05)-and overall survival was poor. Stage I disease showed a much more favorable prognosis than stage II disease. Monomorphic lymphomas had a shorter survival than polymorphic reticulosis (PR) or lymphomas with features of PR. This result in conjunction with the morphologic transition between them suggested that monomorphic lymphoma may represent the most advanced stage in the spectrum of PR, lymphoma with features of PR, and monomorphic lymphoma.
PMCID: PMC3053843  PMID: 1299234
11.  Gastrointestinal malignant lymphoma: a pathologic study of 37 cases in a single Japanese institution 
The author reviewed pathologic features of 37 cases of malignant lymphoma in the gastrointestinal organs in the last 10 years in our pathology laboratory. The current WHO classification was adopted. The 37 cases consisted of 20 males and 17 female, and the age ranged from 46 to 89 years with a median of 69 years. Of the 37 cases, 25 cases (68%) were gastric lymphomas, 6 cases (16%) were small intestinal lymphomas, and 6 cases (16%) were colon lymphomas. Of the 37 cases, 35 cases (95%) were B-cell neoplasms and 2 cases (5%) were T-cell neoplasms. In the 25 gastric lymphomas (male:female=14:11, age range 46-84 years, median 70 years) 11 cases were diffuse large B-cell lymphomas, and 14 cases were extranodal marginal zone B-cell lymphomas (MALT lymphomas). The clinical endoscopic diagnosis was gastritis in 3, gastric ulcer in 3, gastric carcinoma in 7, carcinoid in 1, submucosal tumor in 1, malignant lymphoma in 2, and suspected MALT lymphoma in 8. In the 6 small intestinal lymphomas (male:female=2:4, age range 49-89 years, median 70 years), all cases were located in the ileum. Of the 6 cases, 4 were diffuse large B-cell lymphoma and 2 were peripheral T-cell lymphoma. One case showed multiple lymphomas, and one case was associated with rectal adenocarcinoma and one case with gastric MALT lymphoma. The clinical diagnosis was adenocarcinoma in 2, suspected lymphoma in 2, and ileal tumor in 2. In the 6 colon lymphomas (male:female=4:2, age range 69-86 years, median 74 years), 5 cases were diffuse large B-cell lymphomas and one case was follicular lymphoma. Clinical endoscopic diagnosis was GIST in 1, colon carcinoma in 4, and colon polyp in 1. Cases of Hodgkin’s disease, mantle cell lymphoma, Burkitt lymphoma were not recognized in the present series. In summary, the author reported pathologic features of 37 cases of gastrointestinal malignant lymphoma in our laboratory in the last 10 years.
PMCID: PMC3484413  PMID: 23119230
Malignant lymphoma; gastrointestinal organs
12.  Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue lymphoma 
Gastrointestinal lymphoma is the most common type of extranodal lymphoma, and most commonly affects the stomach. Marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) and diffuse large B-cell lymphoma are the most common histologic types of gastric lymphoma. Despite its increasing incidence, diagnosis of gastric lymphoma is difficult at an earlier stage due to its nonspecific symptoms and endoscopic findings, and, thus, a high index of suspicion, and multiple, deep, repeated biopsies at abnormally and normally appearing sites in the stomach are needed. In addition, testing for Helicobacter pylori (H. pylori) infection and endoscopic ultrasonography to determine the depth of tumor invasion and involvement of regional lymph nodes is essential for predicting response to H. pylori eradication and for assessment of disease progression. In addition, H. pylori infection and MALT lymphoma development are associated, and complete regression of low-grade MALT lymphomas after H. pylori eradication has been demonstrated. Radiotherapy and/or chemotherapy can be used in cases that show poor response to H. pylori eradication, negativity for H. pylori infection, or high-grade lymphoma.
doi:10.3748/wjg.v20.i11.2751
PMCID: PMC3961970  PMID: 24659867
Mucosa-associated lymphoid tissue; Lymphoma; Helicobacter pylori; Eradication; Remission
13.  Sino-nasal T-cell lymphoma invading the brain: A case study 
Lesions occupying the anterior cranial fossa may arise de novo or are extensions from the sino-nasal areas with a handful of differentials in either group. The imaging findings, though to a large extent standardized are not full proof. Primary central nervous system lymphoma and sino-nasal lymphoma are uncommon variants of extranodal non-Hodgkin's lymphoma (NHL). We encountered a 35-year-old lady presenting with headache and seizures with a mass lesion involving the ethmoids with invasion into the anterior cranial fossa diagnosed as T-cell extranodal NHL. Gross total resection and reconstruction of the skull base were done. She was treated with chemotherapy and radiotherapy and is doing well at 6 months follow-up. This is the first report of a sino-nasal T-cell lymphoma invading the brain-parenchyma in an immuno-competent person. Sino-nasal primary T-cell lymphoma presenting as skull base pathology should form an essential differential diagnosis along with other routine lesions of anterior cranial fossa. Since these lesions have a good response to chemo and radiotherapy, a trans-nasal biopsy may obviate the need of a craniotomy if neurosurgeons are aware of this rare entity.
doi:10.4103/1793-5482.146626
PMCID: PMC4323970
Immunohistochemistry; lymphoma; sino-nasal; T-cell
14.  Orbital lymphoma: diagnostic approach and treatment outcome 
Background
Lymphomas of the orbit and orbital adnexae are rare tumors, comprising only 1% of all non-Hodgkin’s lymphoma. The majority of non-Hodgkin’s lymphomas of the orbit are extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue type. Because of nonspecific clinical signs and symptoms, some diagnostic delay may occur. The purpose of the study was to evaluate the diagnostic approach in orbital lymphomas and to analyze their treatment outcome.
Methods
In the period from 2005 to 2012, from a group of 135 patients with tumors of the orbit, we identified 11 patients diagnosed with orbital lymphoma. This patient cohort was reviewed retrospectively.
Results
The patient group consisted of 11 patients (seven females, male males) with a median age of 57.7 years (range 42 to 88 years). Orbital swelling, pain and motility impairment were the leading clinical symptoms. Diagnosis was confirmed by surgical biopsy. Depending on the anatomic location of the tumor, a surgical biopsy was taken using a blepharoplasty incision, a lateral orbitotomy or a navigation-guided biopsy. The predominant histology was extranodal non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue type (82%). All patients underwent complete clinical staging. These were clinical stage IEA in seven patients, and stages IIEA (n = 2) and IIIEA (n = 2) in four patients . Patients in stage IEA were treated with radiation therapy alone, with radiation doses between 25 and 40 Gy, and patients with stage IIEA received systemic chemotherapy with bendamustin/rituximab. Those two patients diagnosed with diffuse large B-cell lymphoma and mantle cell lymphoma received systemic chemotherapy according to the R-CHOP protocol.
Conclusions
Owing to unspecific clinical symptoms, some diagnostic delay may occur in orbital lymphoma. If unspecific orbital symptoms are present, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis. Once diagnosis is established and staging is complete, radiation therapy is the recommended treatment for stage IEA patients. Systemic chemotherapy is indicated in selected stage IIEA patients and in patients with stage IIIEA disease.
doi:10.1186/1477-7819-11-73
PMCID: PMC3616859  PMID: 23506357
Orbital lymphoma; Mucosa-associated lymphoid tissue lymphoma; Radiotherapy
15.  Malignant lymphoma of the urinary bladder: a clinicopathological study of 11 cases 
Journal of Clinical Pathology  2000;53(6):458-461.
Aim—To report the clinical and histological features and outcome of primary and secondary malignant lymphomas of the urinary bladder.
Methods—Eleven cases of malignant lymphoma of the urinary bladder were obtained from the registry of cases at St Bartholomews and the Royal London Hospitals. The lymphomas were classified on the basis of their morphology and immunophenotype, and the clinical records were reviewed.
Results—There were six primary lymphomas: three extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) type and three diffuse large B cell lymphomas. Of the five secondary cases, four were diffuse large B cell lymphomas, one secondary to a systemic follicular follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four patients with secondary lymphoma for whom follow up was available had died of disease within 13 months of diagnosis. Primary lymphomas followed a more indolent course. In one case, there was evidence of transformation from low grade MALT-type to diffuse large B cell lymphoma. The most common presenting symptom was haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours resembling transitional cell carcinoma, and in one case the tumours were multiple. These cases represented 0.2% of all bladder neoplasms.
Conclusions—Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type lymphoma involve transitional epithelium, and their presence in high grade lymphoma suggests a primary origin owing to transformation of low grade MALT-type lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are histologically similar, but the prognosis of the former is favourable.
Key Words: bladder • lymphoma • mucosa associated lymphoid tissue lymphoma
doi:10.1136/jcp.53.6.458
PMCID: PMC1731210  PMID: 10911804
16.  Secondary breast lymphoma diagnosed by vacuum-assisted breast biopsy: a case report 
Introduction
Breast lymphoma, either as a manifestation of primary extranodal disease or as secondary involvement, is a rare malignancy, and its diagnosis, prognosis, and treatment have not been clearly defined. On the other hand, Vacuum-assisted breast biopsy (VABB) is a minimally invasive technique with ever-growing use for the diagnosis of mammographically detected, non-palpable breast lesions.
Case presentation
A symptom-free, 56-year-old woman presented with a non-palpable BI-RADS 4B lesion without microcalcifications. She had a positive family history for breast cancer and a history of atypical ductal hyperplasia in the ipsilateral breast four years ago. She reported having been treated for non-Hodgkin lymphoma 12 years ago. With the suspicion of breast cancer, mammographically guided VABB with 11-gauge probe (on the stereotactic Fisher's table) was performed. VABB made the diagnosis of a non-Hodgkin, grade II, B-cell germinal-center lymphoma. VABB yielded enough tissue for immunohistochemistry/WHO classification.
Conclusion
This is the first case in the literature demonstrating the successful diagnosis of breast lymphoma by VABB, irrespectively of the level of clinical suspicion. It should be stressed that VABB was able to yield enough tissue for WHO classification. In general, lymphoma should never be omitted in the differential diagnosis, since no pathognomonic radiologic findings exist for its diagnosis.
doi:10.1186/1752-1947-1-113
PMCID: PMC2169247  PMID: 17956632
17.  Primary MALT Type Skin Lymphoma—Is ‘Wait and See’ a Possible Strategy? 
Clinical Medicine. Oncology  2008;2:153-158.
Primary cutaneous lymphomas are the second most common site of extranodal non-Hodgkin lymphoma. A specifically type named extranodal marginal zone B-cell lymphomas are indolent low-grade neoplasma.
We report a case of a 42-year-old white man with multiple subcutaneous tumors located on the trunk and neck. The histopathological exam showed a non-epidermotropic, dense lymphocytic infiltrate. Histologic, immunohistochemical and cytologenetic analysis diagnosed primary cutaneous B-cell lymphoma MALT type. Investigation for other extranodal MALT lymphoma gastrointestinal tract, lung, salivary and thyroid glands was negative. The patient refused radiotherapy, but he accepted every 6 months close follow-up. Over a seven years period, we noticed a progressively disappearance of the skin lesions.
The necessity of aggressive treatment of this disease with excellent prognosis is discussed.
The treatment necessity of primary cutaneous B-cell lymphoma MALT type is discussed.
PMCID: PMC3161667  PMID: 21892278
primary cutaneous B-cell lymphoma; MALT type; therapy
18.  Gastrointestinal lymphomas: Morphology, immunophenotype and molecular features 
Primary gastrointestinal lymphoma comprises 10-15% of all non-Hodgkin lymphomas and encompasses 30-40% of the total extranodal lymphomas. Approximately 60-75% of cases occur in the stomach, and then the small bowel, ileum, cecum, colon and rectum. Lymphoid neoplasms may consist of mature B, T and less commonly extranodal NK/T cells. Of these, the two most frequently encountered histologic subtypes are extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), where Helicobacter pylori infection is implicated in a number of cases, and diffuse large B cell lymphoma. Several B cell lymphomas are associated with chromosomal aberrations. Enteropathy-associated T cell lymphoma, type I in particular, usually arises in a background of celiac disease. T cell gene rearrangement confirms clonality. NK/T cell neoplasms are invariably associated with Epstein-Barr virus infection and are often aggressive; thus, differentiation from a benign NK-cell enteropathy is paramount. Although incidence of other hematopoietic malignancies in the gastrointestinal tract such as plasma cell myeloma associated with amyloidosis, plasmablastic lymphoma, Hodgkin disease, histiocytic sarcoma and mast cell sarcoma is extremely rare, these entities have been documented, with the latter two demonstrating aggressive clinical behavior. Endoscopic ultrasonography is an important adjunct in disease staging and follow-up. Conservative antibiotic treatment of stage I MALT lymphomas with associated Helicobacter pylori infection achieves good clinical outcome with high remission rate. Chemotherapy, radiation and rarely surgery are reserved for advanced diseases or cases resistant to conservative therapy and those not associated with Helicobacter pylori infection.
doi:10.3978/j.issn.2078-6891.2012.024
PMCID: PMC3418529  PMID: 22943012
Gastrointestinal lymphomas; MALT lymphoma; NK/T-cell enteropathy
19.  Longlasting Remission of Primary Hepatic Mucosa-associated Lymphoid Tissue (MALT) Lymphoma Achieved by Radiotherapy Alone 
Primary hepatic lymphoma is a rare disorder representing less than 1% of all extranodal lymphomas. Histological examination of a primary hepatic lymphoma usually reveals a diffuse large B-cell lymphoma; there have been few reports of primary hepatic mucosa-associated lymphoid tissue (MALT) lymphomas. A 67-year-old man was being treated for a duodenal ulcer; while receiving therapy for the ulcer, a liver mass was incidentally found on abdominal ultrasonography. The pathologic diagnosis of the hepatic mass was an extranodal marginal zone B-cell lymphoma of MALT. The patient underwent radiotherapy with a total of 4,140 cGy delivered. The patient achieved complete remission and has been followed for 6 years with no recurrence of the disease. This report reviews the case of a primary hepatic extranodal marginal zone B-cell lymphoma of MALT successfully treated by radiotherapy alone.
doi:10.3904/kjim.2006.21.2.127
PMCID: PMC3890736  PMID: 16913444
Primary hepatic lymphoma; Mucosa-associated lymphoid tissue (MALT); Radiotherapy
20.  Primary Spinal Marginal Zone Lymphoma Relapse at a Different Spinal Level after Remission of the Primary Lesion 
Global Spine Journal  2013;3(4):261-264.
Study Design Case report.
Objective Most spinal lymphomas occur in the context of systematic lymphomas. Marginal zone lymphoma (MZL) is a type of B-cell lymphoma originating from the marginal zone of B-cell follicles. Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal MZL and rarely occurs in the central nervous system. To date, there has been only one case report of primary spinal MALT lymphoma and there are no case reports of relapsed MALT lymphoma at a different location of the spine.
Results A 58-year-old man complained of gait disturbance and urinary dysfunction. Magnetic resonance images showed an abnormal lesion in the epidural space at T11–L1 compressing the conus medullaris. The patient underwent laminectomy and partial resection of the tumor. Histopathologic and immunohistochemical findings were consistent with MALT lymphoma. Following postoperative radiotherapy, the epidural mass disappeared completely. Three years later, epidural MALT lymphoma at a different location in the thoracic spine (T8–T10) occurred and caused myelopathy again. Histologic diagnosis of the relapsed tumor was the same as had been seen 3 years previously.
Conclusions This is the first case report of relapsed spinal MALT lymphoma at a different location of the thoracic spine. Though the prognosis of MALT lymphoma is fairly good, careful follow-up is needed to screen any relapse or transformation to a high-grade lymphoma.
doi:10.1055/s-0033-1354249
PMCID: PMC3854575  PMID: 24436880
spinal tumors; epidural tumor; spinal marginal cell lymphoma; MALT lymphoma; thoracic spine
21.  Spontaneous regression of primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) colliding with invasive ductal carcinoma of the breast: a case report 
Malignant lymphomas of the breast, whether they are primary or secondary, are rare diseases, constituting only around 0.1 to 0.15% of the primary neoplasm of the breast. Although the most prevalent histological subtype is diffuse large B-cell lymphoma, primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) also occurs in the breast as in other extranodal sites, comprising about 15% of malignant lymphomas of the breast. In many cases, primary MALT lymphoma of the breast is low grade lymphoma, localized in the breast with indolent behavior and good prognosis. Here we report a case of spontaneous regression of primary MALT lymphoma of the breast. The lymphoma collided with invasive ductal carcinoma in the breast. Both tumors were identified in the Vacora biopsy specimen before the operation. However, the lymphoma disappeared, while the carcinoma remained, in the resected mass. To our knowledge, this is the first case report of spontaneous regression of MALT lymphoma of the breast colliding with breast cancer.
PMCID: PMC4230083  PMID: 25400790
MALT lymphoma; invasive ductal carcinoma; breast; spontaneous regression
22.  Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution 
Diagnostic Pathology  2011;6:77.
Background
The subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China.
Methods
Lymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification.
Results
From January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin.
Conclusions
The lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series.
doi:10.1186/1746-1596-6-77
PMCID: PMC3179701  PMID: 21854649
Distribution; Lymphoma; Subtype; WHO classification
23.  Mantle cell lymphoma presenting as a breast mass 
Journal of Clinical Pathology  2001;54(11):883-886.
Breast lymphoma accounts for less than 1% of all non-Hodgkin's lymphomas (NHLs) and approximately 0.1% of all breast neoplasms. Most breast lymphomas are classified as diffuse large B cell or mucosa associated lymphoid tissue (MALT) lymphomas. The case of a 53 year old woman presenting with a breast mass and found to have mantle cell lymphoma is described. Core biopsy of the breast lesion showed a B cell NHL, probably of large cell type and of high grade. Morphological and immunophenotypic analysis of peripheral blood and bone marrow samples suggested a mantle cell lymphoma (MCL). This was confirmed by the detection of a t(11;14) in the bone marrow aspirate and breast tissue by polymerase chain reaction analysis. There have been no previous reports of an MCL presenting as a breast lump. Because a diagnosis of MCL has prognostic and therapeutic implications, this case highlights the need for an awareness of MCL presenting in this way, and the requirement for specialised investigations in its detection.
Key Words: mantle cell lymphoma • breast lymphoma • cyclin D1 • t(11;14)
PMCID: PMC1731308  PMID: 11684727
24.  Ocular adnexal lymphoma—comparison of MALT lymphoma with other histological types 
AIMS—To correlate histological features of ocular adnexal lymphoma using the revised European American lymphoma classification (REAL), with stage of disease at presentation, treatment modalities, and patient outcome. MALT lymphoma defines an extranodal marginal zone B cell lymphoma as outlined in the REAL classification. Comparison groups of patients included those with primary ocular adnexal MALT lymphoma versus primary ocular adnexal lymphomas of other types, MALT lymphoma versus non-MALT lymphomas (primary and secondary), and primary ocular adnexal lymphoma (MALT lymphomas and other types) versus secondary ocular adnexal lymphomas.
METHODS—A retrospective review of the National Ophthalmic Pathology Laboratory records identified 20 cases of ocular adnexal lymphoma over a 10 year period which were reclassified using appropriate immunohistochemical stains. Patients' medical records were examined for data including stage of the disease at presentation, mode of treatment, and patient outcome.
RESULTS—Among the 20 cases identified 14 had primary ocular adnexal lymphomas. 10 of the primary lymphomas had histological features of MALT lymphoma. One case was a primary ocular adnexal T cell lymphoma, one a follicular centre, follicular B cell lymphoma, and two were large cell B cell lymphomas. Six cases had systemic disease, four large B cell, one follicular centre, follicular B cell, and one mantle cell. A significantly higher proportion of patients with MALT lymphomas had early disease (p = 0.005), initially required local treatment (p = 0.005) and were alive at last follow up (p = 0.001) than those without. Two patients with MALT lymphoma had recurrence of lymphoma which responded to further treatment.
CONCLUSIONS—Patients with primary ocular adnexal MALT lymphomas present with localised disease requiring local treatment and have a better outcome compared with patients with other types. As a small percentage of these tumours recur, patients should be followed up indefinitely.


PMCID: PMC1723071  PMID: 10340987
25.  Risk of non-Hodgkin lymphoma subtypes in HIV-infected people during the HAART era: a population-based study 
AIDS (London, England)  2014;28(15):2313-2318.
Objective
HIV-infected people have greatly elevated risk of non-Hodgkin lymphoma (NHL), particularly the AIDS-defining NHL subtypes: diffuse large B-cell lymphoma, Burkitt lymphoma and primary lymphomas arising in the central nervous system. The goals of this analysis were to comprehensively describe risks of NHL subtypes, especially those not well studied, among HIV/AIDS patients; examine risks specifically in the HAART era; and distinguish risks in HIV-infected individuals prior to diagnosis with AIDS.
Design
Population-based registry linkage study.
Methods
We used data from the US HIV/AIDS Cancer Match Study from 1996 to 2010 (N = 273 705) to calculate standardized incidence ratios (SIRs) comparing subtype specific NHL risks in HIV-infected people to those in the general population, and used Poisson regression to test for differences in SIRs between the HIV-only and AIDS periods.
Results
NHL risk was elevated 11-fold compared to the general population, but varied substantially by subtype. AIDS-defining NHL subtypes comprised the majority, and risks were high (SIRs ≥ 17), but risks were also increased for some T-cell lymphomas (SIRs = 3.6–14.2), marginal zone lymphoma (SIR = 2.4), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (SIR = 3.6), and acute lymphoblastic leuke mia/lymphoma (SIR = 2.4).
Conclusion
HIV-infected people in the HAART era continue to have elevated risk of AIDS-defining NHL subtypes, highlighting the contribution of moderate and severe immunosuppression to their cause. Whereas non-AIDS-defining subtypes are much less common, immunosuppression or other dysregulated immune states likely play a role in the cause of some T-cell lymphomas, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, and acute lymphoblastic leukemia/lym phoma.
doi:10.1097/QAD.0000000000000428
PMCID: PMC4260326  PMID: 25111081
AIDS; AIDS-related; epidemiology; HIV; lymphoma; non-Hodgkin lymphoma

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